RESUMO
Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men. PURPOSE: Intentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known. METHODS: Data from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6-16.3 years after randomization (year 12-16). RESULTS: At year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck (p = 0.0122) but this finding was not observed at the year 12-16 visit. In analyses stratified by gender, bone density loss (%) was greater at the total hip for men in the ILI group than the DSE group at both the year 8 and year 12-16 visits (year 8 p = 0.0263 and year 12-16 p = 0.0062). This finding was not observed among women. CONCLUSION: Long term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00017953. June 21, 2001.
Assuntos
Diabetes Mellitus Tipo 2 , Fraturas Ósseas , Fragilidade , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Densidade Óssea , Fraturas Ósseas/complicações , Estilo de Vida , Redução de PesoRESUMO
AIMS: Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. METHODS: Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. RESULTS: Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with â¼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. CONCLUSIONS: ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.
Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Receptores de Adiponectina/metabolismo , Adiponectina/genética , Alelos , Diabetes Mellitus Tipo 2/genética , Feminino , Variação Genética , Genótipo , Humanos , Incidência , Resistência à Insulina/genética , Masculino , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Modelos de Riscos Proporcionais , Receptores de Adiponectina/genéticaRESUMO
AIM: To assess the effects of 24-week treatment with vildagliptin on measures of beta-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). METHODS: Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of beta-cell function [homeostasis model assessment of beta-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test-derived) measures of beta-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). RESULTS: In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AMDelta) = 10.3 +/- 1.5] and vs. placebo (between-treatment difference in AMDelta = 11.5 +/- 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AMDelta = -0.05 +/- 0.01) and vs. placebo (between-treatment difference in AMDelta = -0.09 +/- 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test-derived parameters, and ISR/G (between-treatment difference in AMDelta = 9.8 +/- 2.8 pmol/min/m(2)/mM, p < 0.001) and the insulinogenic index(0-peak glucose) (between-treatment difference in AMDelta = 0.24 +/- 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. CONCLUSIONS: Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test-derived measures of beta-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov.
Assuntos
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Adamantano/uso terapêutico , Idoso , Biomarcadores/sangue , Glicemia/análise , Peptídeo C/análise , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , VildagliptinaRESUMO
The thermic effect of food at rest, during 30 min of cycle ergometer exercise, and after exercise was studied in eight lean (mean +/- SEM, 10 +/- 1% body fat, hydrostatically-determined) and eight obese men (30 +/- 2% body fat). The lean and obese mean were matched with respect to age, height, weight, and body mass index (BMI) to determine the relationship between thermogenesis and body composition, independent of body weight. All men were overweight, defined as a BMI between 26-34, but the obese had three times more body fat and significantly less lean body mass than the lean men. Metabolic rate was measured by indirect calorimetry under four conditions on separate mornings, in randomized order, after an overnight fast: 3 h of rest in the postabsorptive state; 3 h of rest after a 750-kcal mixed meal (14% protein, 31.5% fat, and 54.5% carbohydrate); during 30 min of cycling and for 3 h post exercise in the postabsorptive state; and during 30 min of cycling performed 30 min after the test meal and for 3 h post exercise. The thermic effect of food, which is the difference between postabsorptive and postprandial energy expenditure, was significantly higher for the lean than the obese men under the rest, post exercise, and exercise conditions: the increments in metabolic rate for the lean and obese men, respectively, were 48 +/- 7 vs. 28 +/- 4 kcal over 3 h rest (P less than 0.05); 44 +/- 7 vs. 16 +/- 5 kcal over 3 h post exercise (P less than 0.05); and 19 +/- 3 vs. 6 +/- 3 kcal over 30 min of exercise (P less than 0.05). The thermic effect of food was significantly negatively related to body fat content under the rest (r = -0.55), post exercise (r = -0.66), and exercise (r = -0.58) conditions. The results of this study indicate that for men of similar total body weight and BMI, body composition is a significant determinant of postprandial thermogenesis; the responses of obese are significantly blunted compared with those of lean men.
Assuntos
Temperatura Corporal , Peso Corporal , Alimentos , Obesidade/fisiopatologia , Esforço Físico , Tecido Adiposo/fisiologia , Adulto , Metabolismo Basal , Composição Corporal , Superfície Corporal , Metabolismo Energético , Humanos , Masculino , Obesidade/metabolismo , Descanso , Fatores de TempoRESUMO
The effect of autonomic denervation on the metabolic and hormonal responses during intracellular glucopenia in man was investigated. 2-Deoxy-d-glucose (2 DG), a competitive inhibitor of glucose metabolism, was administered intravenously to nine normal volunteers and to five patients, three with complete cervical cord transection (C-6) and two with idiopathic orthostatic hypotension. Before, during, and after a 20 min infusion of 2 DG (50 mg/kg) plasma concentrations of glucose, lactate, FFA, total catecholamines, immunoreactive insulin (IRI), human growth hormone (HGH), and cortisol were determined for periods up to 150 min. In control subjects, the initial elevation of FFA, glucose. HGH, and cortisol corresponded with the rise in total catecholamines, with maximal levels attained at 60 min, lactate rose at a slower rate, reaching peak levels at 150 min: although no change in IRI was noted. In contrast, 2 DG-induced glucopenic stress in the autonomic denervated subjects was characterized by no detectable catecholamine release or significant rise in glucose, FFA, lactate, or IRI. However, HGH and cortisol responses in four of the five patients were of a similar or greater magnitude than controls.These studies demonstrate that the integrity of the sympathoadrenomedullary axis is essential for the counter-regulatory response to intracellular glucopenia in man. Cortisol and HGH have no apparent role in these events.
Assuntos
Medula Suprarrenal/fisiologia , Glucose/metabolismo , Sistema Nervoso Simpático/fisiologia , Adulto , Antígenos/análise , Glicemia , Catecolaminas/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/administração & dosagem , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Hipoglicemia/induzido quimicamente , Injeções Intravenosas , Insulina/sangue , Lactatos/sangue , Masculino , Ácidos Nicotínicos/farmacologia , Traumatismos da Medula Espinal/metabolismo , Fatores de TempoRESUMO
To clarify the independent relationships of obesity and overweight to cardiovascular disease risk factors and sex steroid levels, three age-matched groups of men were studied: (i) 8 normal weight men, less than 15% body fat, by hydrostatic weighing; (ii) 16 overweight, obese men, greater than 25% body fat and 135-160% of ideal body weight (IBW); and (iii) 8 overweight, lean men, 135-160% IBW, but less than 15% fat. Diastolic blood pressure was significantly greater for the obese (mean +/- SEM, 82 +/- 2 mmHg) than the normal (71 +/- 2) and overweight lean (72 +/- 2) groups, as were low density lipoprotein levels (131 +/- 9 vs. 98 + 11 and 98 + 14 mg/dl), the ratio of high density lipoprotein to total cholesterol (0.207 +/- 0.01 vs. 0.308 +/- 0.03 and 0.302 +/- 0.03), fasting plasma insulin (22 +/- 3 vs. 12 +/- 1 and 13 +/- 2 microU/ml), and the estradiol/testosterone ratio (0.076 +/- 0.01 vs. 0.042 +/- 0.02 and 0.052 +/- 0.02); P less than 0.05. Estradiol was 25% greater for the overweight lean group (40 +/- 5 pg/ml) than the obese (30 +/- 3 pg/ml) and normal groups (29 +/- 2 pg/ml), P = 0.08, whereas total testosterone was significantly lower in the obese (499 +/- 33 ng/dl) compared with the normal and overweight, lean groups (759 +/- 98 and 797 +/- 82 ng/dl). Estradiol was uncorrelated with risk factors and the estradiol/testosterone ratio appeared to be a function of the reduced testosterone levels in obesity, not independently correlated with lipid levels after adjustment for body fat content. Furthermore, no risk factors were significantly different between the normal and overweight lean groups. We conclude that (a) body composition, rather than body weight per se, is associated with increased cardiovascular disease risk factors; and (b) sex steroid alterations are related to body composition and are not an independent cardiovascular disease risk factor.
Assuntos
Composição Corporal , Peso Corporal , Doenças Cardiovasculares/etiologia , Hormônios Esteroides Gonadais/sangue , Adulto , Colesterol/sangue , Eletrocardiografia , Métodos Epidemiológicos , Estradiol/sangue , Teste de Esforço , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Obesidade/complicações , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangueRESUMO
The putative blunted thermogenesis in obesity may be related to insulin resistance, but insulin sensitivity and obesity are potentially confounding factors. To determine the independent effects of obesity and insulin resistance on the thermic effect of food, at rest and after exercise, lean and obese men were matched at two levels of insulin sensitivity determined by insulin-stimulated glucose disposal (milligrams per kilogram fat-free mass [FFM] per minute) during the euglycemic, hyperinsulinemic (40 mU/m2.min) clamp: 5.4 mg/kg FFM for the lean and obese groups with low insulin sensitivity, and 8.1 mg/kg FFM for the groups with high insulin sensitivity. The two lean groups were matched for percent fat (approximately 15 +/- 1% fat), as were the two obese groups (approximately 33 +/- 2% fat). Energy expenditure was measured for 3 h in the fasting state and for 3 h after a 720-kcal mixed meal, each at rest and immediately after 1 h of cycling at 100 W. The thermic effect of food (TEF) was calculated as the postprandial minus fasting energy expenditure (kcal/3 h) during rest and after exercise. During rest, TEF was blunted by both obesity (24 +/- 5 and 34 +/- 6 kcal/3 h for obese groups with low and high insulin sensitivity vs. 56 +/- 6 and 74 +/- 6 kcal/3 h for the lean groups with low and high insulin sensitivity; P less than 0.01 lean vs. obese) and insulin resistance (insulin-resistant less than insulin-sensitive, at both levels of obesity; P less than 0.01). After exercise, TEF was also impaired in the obese (47 +/- 6 and 44 +/- 5 kcal/3 h for the insulin-resistant and -sensitive groups) and in the lean insulin-resistant (55 +/- 5 kcal/3 h), compared with the lean insulin-sensitive men (71 +/- 3 kcal/3 h), P less than 0.01. Compared with rest, TEF after exercise was improved, but not normalized, in both obese groups (P less than 0.05), but unchanged in the lean groups. These results suggest that both insulin resistance and obesity are independently associated with impaired TEF at rest, but the responsiveness of thermogenesis to exercise before a meal is related to the obese state and not independently to insulin resistance per se.
Assuntos
Regulação da Temperatura Corporal , Resistência à Insulina , Obesidade/fisiopatologia , Adulto , Exercício Físico , Alimentos , Glucose/farmacologia , Humanos , Masculino , RespiraçãoRESUMO
An interdisciplinary panel of specialists met in Mallorca in the first European Symposium on Morbid Obesity entitled; "Morbid Obesity, an Interdisciplinary Approach". During the two and half days of the meeting, the participants discussed several aspects related to pathogenesis, evaluation, and treatment of morbid obesity. The expert panel included basic research scientists, dietitians and nutritionists, exercise physiologists, endocrinologists, psychiatrists, cardiologists, pneumonologists, anesthesiologists, and bariatric surgeons with expertise in the different weight loss surgeries. The symposium was sponsored by the Balearic Islands Health Department; however, this statement is an independent report of the panel and is not a policy statement of any of the sponsors or endorsers of the Symposium. The prevalence of morbid obesity, the most severe state of the disease, has become epidemic. The current recommendations for the therapy of the morbidly obese comes as a result of a National Institutes of Health (NIH) Consensus Conference held in 1991 and subsequently reviewed in 2004 by the American Society for Bariatric Surgery. This document reviews the work-up evaluation of the morbidly obese patient, the current status of the indications for bariatric surgery and which type of procedure should be recommended; it also brings up for discussion some important real-life clinical practice issues, which should be taken into consideration when evaluating and treating morbidly obese patients. Finally, it also goes through current scientific evidence supporting the potential effectiveness of medical therapy as treatment of patients with morbid obesity.
Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Obesidade Mórbida/terapia , Guias de Prática Clínica como Assunto/normas , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Europa (Continente) , Humanos , Estados UnidosRESUMO
BACKGROUND/OBJECTIVES: The objective of this study was to compare the measurement of areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) with the measurement of volumetric bone mineral density (vBMD) by high-resolution peripheral computerized tomography (HR-pQCT) in subjects with a wide range of body mass indices (BMI). SUBJECTS/METHODS: We scanned the arms and legs of 49 premenopausal women, aged 21-45 years, with BMI from 18.5 to 46.5, by HR-pQCT and found that there was a nonsignificant change in vBMD associated with increased BMI, whereas aBMD (DXA) was associated with a positive significant increase. HR-pQCT scans a slice at the extremity of the tibia and radius, whereas DXA scans the entire leg and arm. RESULTS: The correlation coefficients (r) of BMD (DXA) of the legs with BMI were 0.552, P<0.001, with %fat it was 0.378, P<0.01 and with W it was 0.633, P<0.001. The r of BMD (DXA) of the arms with BMI was 0.804, P<0.001, with %fat it was 0.599, P<0.001 and with W it was 0.831, P<0.001, whereas the r of the average bone density (D100) of legs and arms measured by HR-pQCT with BMI, W and %fat were not significant. CONCLUSIONS: Although HR-pQCT and DXA scan different parts of the bone, the high r of BMD with BMI and low r of bone density measured by HR-pQCT with BMI suggest that BMD measured by DXA is artifactually increased in the presence of obesity.
Assuntos
Absorciometria de Fóton , Densidade Óssea , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Estatura , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa/metabolismo , Rádio (Anatomia)/ultraestrutura , Tíbia/ultraestrutura , Adulto JovemRESUMO
Sympathetic responses were evaluated in rats transplanted with neonatal pancreatic tissue. Transplantation was by one of two methods: mild collagenase digestion with subsequent intraportal injection, or direct placement of intact pancreatic tissue under the renal capsule. Compared with control intact animals, both groups of transplanted rats reverted to normal fasting and postglucose load plasma glucose and insulin. The hyperglycemia characteristic of stress or of injected exogenous epinephrine was present and similar in all three groups. The response to an intragastric glucose load or to tolbutamide injection during stress was similar in transplanted and in control animals. All three groups of rats responded to sustained cortisol injection with a compensatory hyperinsulinemia but maintained normal plasma glucose, water intake, and urine volume. No evidence could be detected in this study of an exaggerated "denervated" response of the transplanted islets. The normal sympathetic responses of these neonatal islet preparations in which little or no collagenase was used, in comparison with the abnormal responses previously reported for collagenase-treated individually isolated adult rat islets, suggest differences in recuperative powers of the sympathetic innervation in islets, possibly related to age and to method of preparation of transplanted tissue.
Assuntos
Epinefrina/farmacologia , Hidrocortisona/farmacologia , Ilhotas Pancreáticas/fisiologia , Animais , Glicemia/metabolismo , Técnicas de Cultura , Insulina/sangue , Insulina/metabolismo , Ilhotas Pancreáticas/inervação , Transplante das Ilhotas Pancreáticas , Masculino , Ratos , Ratos Endogâmicos Lew , Estresse Fisiológico/metabolismo , Estresse Fisiológico/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Tolbutamida/farmacologiaRESUMO
Twenty-four volunteers, mean age 78, including eight mildly non-insulin-dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol > 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium-poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromium repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.
Assuntos
Glicemia/metabolismo , Candida , Cromo/uso terapêutico , Lipídeos/sangue , Saccharomyces cerevisiae , Idoso , Colesterol/sangue , Diabetes Mellitus/sangue , Teste de Tolerância a Glucose , Humanos , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
For Caucasian women, an excess of abdominal fat is a potent risk factor for the development of diabetes and cardiovascular disease. However, there is limited information regarding the health risks of upper body obesity for African-American women despite a higher prevalence of obesity and obesity-related diseases and a reportedly higher prevalence of abdominal fat accumulation. This study aimed to determine whether UBO, independent of total body fatness, is as potent a diabetic and CVD risk factor for black women as has been confirmed for white women. Diabetes and CVD risks and androgenic status were assessed in nondiabetic, premenopausal women of similar body fatness who differed by race (black or white) and body fat distribution (UBO or lower body obesity). In black women, high-density lipoprotein cholesterol was the only measurement adversely affected by abdominal fat; HDL cholesterol was significantly lower in the black UBO group (1.14 +/- 0.05 mM) compared with the black LBO group (1.37 +/- 0.08 mM). This contrasts markedly with our findings in white women. In confirmation of previous reports, white UBO women, compared with white LBO counterparts, had significantly higher glucose (967.6 vs. 709.2 mM/2 h) and insulin (120.5 vs. 52.1 pM/2 h) areas and significantly lower peripheral insulin sensitivities (0.99 vs. 2.95 x 10(-4) min-1/microU/ml). In addition, HDL cholesterol levels were significantly lower in the white UBO group (1.03 mM) compared with the white LBO group (1.49 mM), whereas plasma TG levels (white UBO, 1.72 vs. white LBO, 0.88 mM) and dBPs (white UBO, 84 vs. white LBO, 75 mmHg) were significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Tecido Adiposo/anatomia & histologia , População Negra , Glicemia/metabolismo , Lipídeos/sangue , Obesidade/fisiopatologia , População Branca , Adulto , Análise de Variância , Antropometria , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Peso Corporal , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Feminino , Hormônio Foliculoestimulante/sangue , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Obesidade/complicações , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Triglicerídeos/sangueRESUMO
Culture of islets isolated from the pancreas of neonatal rats successfully preserved function for 6 days, as indicated by release of insulin into the culture medium and reversal of experimental diabetes bu cultured islet isografts. Release of insulin into the culture medium correlated with lowering of fasting blood glucose in the diabetic recipient. Intravenous glucose tolerance was normal in recipients of immediate and 24-h cultured islets but abnormal in recipients of 6-day cultured islets. Culture of the islets isolated from human pancreases (cadaveric) resulted in islet purification but at the expense of loss of islets, with only 1--5% surviving 1 wk of culture. During 8--10 days in culture, insulin release declined, and histological examination revealed only a few viable islets. Islets isolated from surgical specimens survived the culture conditions as demonstrated by viable cell clumps and insulin secretion. After an 85% pancreatectomy in the patient with chronic pancreatitis, islets were isolated, cultured for 7 days, and then autografted into muscle pockets and the subcutaneous space of the forearm. There was no evidence of function.
Assuntos
Transplante das Ilhotas Pancreáticas , Animais , Glicemia/metabolismo , Sobrevivência Celular , Células Cultivadas , Sobrevivência de Enxerto , Humanos , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Ratos , Ratos Endogâmicos Lew , Transplante IsogênicoRESUMO
Our previous finding that a waist-to-hip ratio (WHR) >0.85 was not associated with similar health risks in black, compared with white, obese premenopausal non-diabetic women of similar fatness is attributed to either 1) a different relationship between WHR and visceral adiposity or 2) differences in the relationship between visceral adiposity and the metabolic abnormalities of obesity. We measured visceral (VAT) and subcutaneous adipose tissue (SCAT) areas at midwaist in 25 black and 25 white obese nondiabetic pre-menopausal women with similar BMI, percentage body fat, and wide range of WHR (0.7-0.95 for black women and 0.7-0.9 for white women) and then compared insulin sensitivity index (SI), glucose and insulin areas under the 2-h curve (AUCs) during an oral glucose tolerance test (OGTT), and blood lipids in the two groups before and after adjustments for total body and visceral adiposity. After adjusting for total body fat mass (FM), obese black women had significantly less VAT (by 32 cm2) and lower VAT/SCAT for any given WHR. The regression equations predicting the SI the glucose and insulin AUCs, and the triglyceride and HDL cholesterol levels from regional adipose tissue measurements (VAT, SCAT, or VAT/SCAT) and from total body fat (FM or percentage body fat) had slopes that were not significantly different for black and white women. LDL cholesterol levels were independently related to VAT in black but not in white women. The black women had a similar SI insulin AUC, and triglyceride levels but significantly lower glucose AUC and higher HDL cholesterol levels (P < 0.001), after adjusting for VAT and FM. Regression analysis of the pooled data showed that high VAT and high VAT/SCAT, but not SCAT, predicted lower SI higher glucose and insulin AUCs during OGTT, and higher triglyceride levels, independent of total adiposity. We conclude that while increases in VAT and VAT/SCAT adversely affect metabolism in both black and white obese premenopausal women, similar levels of total body and visceral adiposity are associated with different metabolic risk factors in these groups.
Assuntos
Tecido Adiposo/anatomia & histologia , População Negra , Composição Corporal , Obesidade/fisiopatologia , Pré-Menopausa , Medição de Risco , População Branca , Adulto , Negro ou Afro-Americano , Análise de Variância , Glicemia/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Lipídeos/sangue , Análise de Regressão , Pele , VíscerasRESUMO
Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.
Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus/genética , Variação Genética , Obesidade/genética , Receptores de Peptídeos/genética , Adolescente , Adulto , Substituição de Aminoácidos , Animais , Índice de Massa Corporal , Clonagem Molecular , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Isoleucina , Masculino , Metionina , Camundongos , Pessoa de Meia-Idade , Linhagem , Polimorfismo Conformacional de Fita Simples , Receptor Tipo 4 de Melanocortina , Receptores de Peptídeos/química , Proteínas Recombinantes/química , Treonina , ValinaRESUMO
Resting metabolic rate was measured in a group of 22 women of normal body weight with bulimia nervosa and in 19 age-, sex-, and weight-matched control subjects. Mean resting metabolic rate of patients was significantly lower than that of controls (5162 +/- 928 vs 5636 +/- 449 kJ/24 h [1229 +/- 221 vs 1342 +/- 107 kcal/24 h]), as was mean fasting blood glucose level (4.0 +/- 0.6 vs 4.6 +/- 0.6 mmol/L). Mean basal thyrotropin level was significantly lower in patients than controls, but other thyroid indexes did not differ. There were no group differences in body fat mass, fat cell size, or lipoprotein lipase activity. These data suggest that there is a disturbance in energy regulation in bulimia nervosa. However, the origins and role of this disturbance in the pathophysiology of bulimia are unclear.
Assuntos
Anorexia Nervosa/metabolismo , Bulimia/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/enzimologia , Adulto , Anorexia Nervosa/complicações , Metabolismo Basal , Glicemia/análise , Composição Corporal , Peso Corporal , Bulimia/complicações , Metabolismo Energético , Feminino , Humanos , Lipase Lipoproteica/metabolismo , Tireotropina/sangueRESUMO
OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons. DESIGN: In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN OUTCOME MEASURES: The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta , Preferências Alimentares , Alimentos Fortificados , Obesidade/dietoterapia , Redução de Peso , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Hemodinâmica/fisiologia , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Obesidade/complicações , Cooperação do Paciente , Qualidade de Vida , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. OBJECTIVE: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. METHODS: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. RESULTS: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean differences (+/-SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-group P values), respectively, were as follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02); diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, -0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/- 21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/- 0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg; and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly improved for daily and work activities (P < .05) and nutritional health perceptions (P < .05) with the CCNW plan relative to the self-selected group. Overall nutrient intake and compliance were both significantly (P < .001) better with the CCNW plan. CONCLUSIONS: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease.
Assuntos
Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/etiologia , Dietoterapia , Adulto , Idoso , Pressão Sanguínea , Peso Corporal , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Carboidratos da Dieta/metabolismo , Feminino , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de RiscoRESUMO
Diabetes mellitus is more prevalent in the American Black population than in the White population. The prevalence is increasing in Blacks, and there is evidence that it is accompanied by a greater severity of diabetic complications. In addition, mortality figures are higher in Blacks, and Black women are more seriously affected than Black men. Although the reasons for this are unclear, some factors stand out as important. These include obesity, socioeconomic status, and genetics. Obesity is a severe problem in Blacks, particularly in women. Both the degree and the distribution of fat may contribute greatly to the prevalence of diabetes in Blacks. Although the prevalence of obesity is higher in the poor economic groups, multivariate analysis suggests that poverty cannot explain all of the excess obesity that occurs in the Black population. More research is needed into a possible genetic predisposition of Blacks to obesity and diabetes and into the interrelationship between the two conditions in this racial group.
Assuntos
População Negra , Diabetes Mellitus/epidemiologia , Fatores Etários , Demografia , Humanos , Obesidade/epidemiologia , Prevalência , Estados Unidos/epidemiologia , População BrancaRESUMO
Recent recommendations for the dietary management of diabetes mellitus state that diet needs to be individualized so that there is improved glucose and lipid control in the patient. In a majority of individuals with diabetes, this is best done with a diet that is low in fat and high in carbohydrate, particularly that of cereal origin. However, symptoms of hyper- and hypoglycemia must be averted. Most cereal products, however, tend to have a high glycemic index Cereals such as Prowashonupana barley or fractions of oat bran are particularly high in the soluble fiber beta-glucan, which when taken with a meal increases the viscosity of the meal bolus once it has reached the small intestine, where the absorption of nutrients occurs. This high viscosity delays absorption. A 50% reduction in glycemic peak can be achieved with a concentration of 10% beta-glucan in a cereal food. A significant lowering of plasma LDL cholesterol concentrations can also be anticipated with the daily consumption of > or = 3 g of beta-glucan. Diabetic individuals can benefit from diets that are high in beta-glucan, which, as a component of oats and barley, can be incorporated into breakfast cereals and other products.